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Effect of intranasal fluticasone on cellular infiltration, endothelial adhesion molecule expression, and proinflammatory cytokine mRNA in nasal polyp disease.

BACKGROUND: Nasal polyp (NP) disease demonstrates a gradual response to treatment with intranasal steroids. We hypothesized that various inflammatory features that promote NP eosinophilia would show a differential sensitivity to treatment with intranasal fluticasone. OBJECTIVES: We conducted a double-blind, placebo-controlled trial of 4 weeks of intranasal fluticasone propionate or matching placebo to assess their effectiveness in reducing NP inflammatory cells, expression of endothelial vascular cell adhesion molecule (VCAM)-1 and P-selectin, and expression of cytokines involved in induction of a group of adhesion molecules (ie, IL-4, IL-13, TNF-alpha, and IL-1beta). METHODS: Twenty subjects (9 women and 11 men) with severe chronic sinusitis and NP were studied. Systemic and intranasal steroids were withheld for a minimum of 1 month and 2 weeks, respectively, before the study. Biopsy specimens of NPs were obtained 1 week before and 4 weeks after treatment with intranasal fluticasone 100 microg or placebo per nostril administered twice daily. Biopsy specimens were snap frozen for immunostaining or fixed in paraformaldehyde for in situ hybridization. Pretreatment to posttreatment results were analyzed with Wilcoxon's signed-rank test. RESULTS: Fluticasone treatment significantly reduced NP eosinophilia (P =.02) and CD4(+) T lymphocytes (P =.02). Eosinophils expressing the marker EG2 were more significantly reduced (P =.007). Fluticasone also reduced the expression of P-selectin (P =.005) and the number of IL-4 and IL-13 mRNA+ cells (P =.02 and.05, respectively). In contrast, fluticasone did not significantly reduce expression of endothelial VCAM-1 or the number of TNF-alpha or IL-1beta mRNA+ cells in the polyps. CONCLUSIONS: We conclude that intranasal fluticasone reduced NP inflammation but that expression of proinflammatory cytokines and endothelial VCAM-1 were relatively unaffected by fluticasone treatment. These latter inflammatory features may contribute to the persistence of NP disease despite intranasal steroid treatment.

Administration, Intranasal↗

[Epithelial cell proliferation in nasal polyps].

The mechanism stimulating the growth of nasal polyps remains unclear. The fact that nasal polyps formation is connected with increase of the epithelial surface suggests that the dysregulation of epithelial cell proliferation takes part in their pathogenesis. Furthermore, macroscopically nonsuspected nasal polyp, usually benign tissue lesion, occasionally may be misdiagnosed such as neoplasm. Only a few studies have undertaken the subject of cell proliferation in nonneoplastic respiratory epithelium. We examined 30 nasal polyps specimens by immunohistochemistry to recognize the expression of nuclear antigen present in proliferating cells, using rabbit anti-human Ki-67 antigen. Our study revealed significantly higher Ki-67 index in nasal polyps than in nasal mucosa (p < 0.005, tab.I). Based on this findings it seems that increased epithelial cell proliferation and chronic inflammation generate the lesion of the nasal mucosa leading to nasal polyps formation.

Cell Proliferation↗

IL-5 synthesis is upregulated in human nasal polyp tissue.

BACKGROUND: In most nasal polyps, tissue eosinophilia is a striking finding, the pathologic mechanism of which is not understood. OBJECTIVE: This study was performed to investigate a possibly distinct cytokine and chemokine pattern that could explain the characteristic tissue eosinophilia in nasal polyps. METHODS: Polyps from 23 patients and turbinate tissue from 18 control subjects were investigated. The cytokine protein content (IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, IL-1RA, RANTES, GRO-alpha) of tissue homogenates was measured by ELISA. Immunohistochemistry was performed in selected samples to detect IL-5+, major basic protein-positive, and EG2+ cells. RESULTS: IL-5 was detectable in only one sample of tissue from 18 control subjects but was found in 18 of 23 nasal polyps. Immunohistochemistry revealed an abundant number of IL-5+ cells, of which 69.5% could be identified as eosinophils by morphology. IL-6, IL-8, IL-10, tumor necrosis factor-alpha, GRO-alpha, and RANTES were detected in all specimens, without significant differences between groups (p > or = 0.05), whereas significnatly higher concentrations of IL-1 beta and IL-1RA were found in turbinate mucosa (p < or = 0.05). IL-3 was not detectable: granulocyte-macrophage colony-stimulating factor could only occasionally be found. CONCLUSION: This study indicates that IL-5 plays a key role in the pathophysiology of eosinophilic nasal polyps and may be produced by eosinophils.

Adult↗

Increased expression of matrix metalloproteinase-2 in nasal polyps.

OBJECTIVE: The formation and growth of nasal polyps requires remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can collectively degrade almost all extracellular matrix components. The aim of this study was to investigate the role of MMPs in nasal polyps. MATERIAL AND METHODS: The expression of MMP-2 and -9 was investigated in the nasal polyps of 20 patients undergoing endonasal sinus surgery and compared with that in control nasal mucosal samples obtained from 20 non-allergic hypertrophic rhinitis patients. Tissue samples were either homogenized for reverse transcriptase polymerase chain reaction analysis or frozen for immunohistochemistry. RESULTS: MMP-2 mRNA expression was observed only in the nasal polyp samples and not in the control tissues. MMP-9 mRNA was not expressed in either type of tissue. Similarly, MMP-2 expression was observed in the nasal polyps of chronic sinusitis patients but not in the inferior turbinate mucosa of the control subjects. MMP-2 positivity was present in basal cells in the surface epithelium and in infiltrating cells in subepithelial tissues. MMP-9-positive cells were not observed in either nasal polyps or inferior turbinates. These results suggest that MMP-2 expression is characteristic of nasal polyps. CONCLUSION: MMP-2 may play a role in the remodeling of nasal polyps.

Actins↗

[Clinical and pathological observation of recurrent nasal polyp formation].

To investigate the mechanism of nasal polyp recurrence, 19 patients with recurrent nasal polyp were retrospectively analysed. In 4 patients, nasal polyp specimens had been sent for pathological examination more than three times, and in 6 patients, bacteria culture was performed. There were two types of recurrent nasal polyp: water-cyst type (fast recurrence) and edematous granulation type (slow recurrence). Both types were the result of inflammatory reaction, perhaps related to trauma of operation. Water-cyst formation indicated stronger inflammatory reaction. During follow-up, 10 patients were cured and 9 recurred. Preventive measures against nasal polyp recurrence were discussed.

Adult↗

[The infiltration and activation stage of eosinophils in nasal polyps].

OBJECTIVE: To assess the infiltration and activation of eosinophils in nasal polyps. METHOD: Nasal polyps from sixteen patients were investigated. The samples were stained with Chromotrope 2R histochemical and ABC immunohistochemical methods. RESULT: The majority of eosinophils in nasal polyps were activated, and there were no significant differences in the numbers of total eosinophils (Chromotrope 2R positive cells) and activated eosinophils (EG2 positive cells) between allergic and nonallergic patients. CONCLUSION: Eosinophilia is a prominent histologic feature of nasal polyps which indicates that the activated eosinophils may play vital role in the pathogenesis of nasal polyps.

Adult↗

Trace elements in nasal polyps.

The reason why nasal polyps occur has not been explained yet. In the literature, the role of immunological factors are considered and broadly discussed, but there is no information on the role of microelements in the pathogenesis of nasal sinusal polyposis. In this study, concentrations of Cu, Se, Zn, and Pb in tissue of nasal polyps were determined. The tissue samples were taken from 41 patients during polypectomia procedures, whereas healthy tissue from nasal mucosa was sampled from 10 patients during endonasal surgery. The concentrations of the elements were determined by atomic absorption spectrometry. It was found that the concentrations of all the elements were signifcantly lower in polyp tissues than in healthy nasal mucosa. The reasons for this are unclear in the present study.

Adolescent↗

Interferon gamma expression in human nasal polyps.

One feature among nasal polyps (NPs) is the predominance of lymphocytes and eosinophils. We hypothesize that elevated levels of interferon gamma (IFN-gamma) activate lymphocytes and eosinophils within the NP microenvironment. Nasal polyps were evaluated for distribution and levels of IFN-gamma in specimens from 27 patients with nasal polyposis and 4 controls. Immunohistochemical study revealed IFN-gamma staining of eosinophils, glandular cells, and epithelium (27 of 27 patients). ELISA analysis indicated elevated IFN-gamma levels in total NP tissues (25.6 +/- 7.23 pg/mg total protein [TP]) compared with controls (16.27 +/- 6.54 pg/mg TP). Three subpopulations were identified based on IFN-gamma levels: low IFN-gamma group (10.7 +/- 5.51 pg/mg TP); medium IFN-gamma group (25.70 +/- 5.90 pg/mg TP); and high IFN-gamma group (52.58 +/- 10.29 pg/mg TP). The latter levels were approximately 3.5 times the control levels (P<0.0025). Patients with previous polypectomy surgery showed higher levels of IFN-gamma compared with controls (P<0.0423). A trend was found with increased IFN-gamma levels and allergy, asthma, and topical steroid use.

Adult↗

Nasal polyps in identical twins.

Nasal polyps are multifactorial in aetiology but are associated with respiratory diseases, particularly late onset asthma. Several members of a family may be affected with nasal polyps but there is little evidence for a genetic basis for this. Some evidence to support a genetic predisposition comes from the development of polyps in identical twins.

Diseases in Twins↗

Regulation of immunoglobulin secretion by plasma cells infiltrating nasal polyps.

OBJECTIVE/HYPOTHESIS: To learn more about the role of plasma cells infiltrating nasal polyps in the pathogenesis of nasal polyposis, we examined their function by analyzing immunoglobulin (Ig) production and the factors implicated in the secretion. STUDY DESIGN: A series of 19 consecutive nasal polyp tissue samples and, as a control, peripheral blood samples from the same patients, were studied by histopathological and immunological examination. METHODS: Hematoxylin-eosin and immunohistochemical staining was carried out to identify plasma cells infiltrating nasal polyps. Nasal polyp mononuclear cells (NPMNCs) were purified from nasal polyp tissue samples, and Ig-secreting cells were identified in cytospin preparations stained with fluorescein isothiocyanate-conjugated antibodies against IgA, IgG, IgM, and IgE. Purified NPMNCs were cultured in basal conditions and after the addition of several stimuli. Ig secreted into the culture supernatants was evaluated by an enzyme-linked immunosorbent assay. RESULTS: Plasma cells accounted for an important fraction of the inflammatory infiltrate. The main Ig isotype synthesized by these cells was IgA, whereas little IgE was detected. In vitro cultures demonstrated that the plasma cells actively secreted Ig for a short period. When cytokine dependence was analyzed, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) were shown to be partially responsible for the Ig production. Dependence on CD95-mediated apoptosis was not observed. CONCLUSIONS: Nasal polyp-infiltrating plasma cells are mainly IgA-secreting cells, the latter property being related to the mucosal immune system. The IgA production is partly dependent on IL-10 and TNF-alpha. The absence of IgE-secreting cells in most of the samples suggests that a type I hypersensitivity reaction is not essential for the development of nasal polyp.

Adolescent↗

Study of nasal surface basophilic cells in patients with nasal polyp.

Surface basophilic cells in samples obtained from the inferior concha of nasal polyp patients were examined microscopically. Although the cells were believed to be specific to nasal allergy patients, we were also able to observe them in nasal polyp patients without nasal allergy. These cells were found in 5% of normal controls, in 14% of patients with chronic sinusitis without nasal polyp, in 65% with nasal polyp and in 91% with nasal allergy. In patients with unilateral nasal polyp the surface basophilic cells increased on the side with nasal polyp but not on the side without nasal polyp. As the nasal polyp grew in size, so the number of cells grew. After the polyp was removed, the cells decreased appreciably in number. With regard to other nasal diseases, surface basophilic cells were observed in 80% of tracheotomized patients, in 88% of laryngectomized patients due to laryngeal cancer, in 100% of patients with a tumor in nasal cavity, in 100% of patients with irradiation treatment of the nasal cavity and in 90% of patients with atrophic rhinitis. The surface basophilic cells seem to increase in number through some mechanism induced by a blockage of nasal airway by nasal polyp.

Basophils↗

Nasal polyps: a manifestation of allergy?

The cause of nasal polyps is speculative. In the 1930s nasal polyps were considered to be a manifestation of allergy. This theory was challenged in the 1970s. Many patients with nasal polyps have no identifiable allergic disease. The purpose of this study is to better define the relationship between allergy and nasal polyps. Twelve patients with nasal polyps were evaluated by history, physical examination, skin testing, nasal smear for eosinophils, specific IgE determination from serum, nasal secretions, and nasal polyp fluid. Similar data were collected from three control groups: (1) 10 patients with allergic rhinitis, (2) 10 patients with nonallergic rhinitis, and (3) 10 patients with no known nasal disease. By comparing the incidence of markers for allergic disease in patients with nasal polyposis to each of the three control groups, the role of allergic disease in nasal polyposis was delineated.

Adult↗

Quantitative glycohistochemical characterization of normal nasal mucosa, and of single as opposed to massive nasal polyps.

A series of 41 nasal polyps (23 single and 18 massive) and 6 normal nasal mucosa specimens was glycohistochemically investigated. Five plant lectins were used, i.e., the peanut agglutinin (PNA), the wheat germ agglutinin (WGA), the gorse seed agglutinin (UEA-I), the Maackia amurensis agglutinin (MAA), and the elderberry bark agglutinin (SNA). A neoglycoconjugate and 2 animal lectins (CL-14 and CL-16) were also used. Three quantitative features were calculated by means of computer-assisted microscopy: the percentage of tissue area specifically stained by the histochemical probe, the staining intensity, and the heterogeneity level of the staining distribution. The results show that with respect to sialic acid-glycoprotein binding characteristics as determined by SNA, MAA, and WGA probes, the normal nasal mucosa differed markedly (p<.00001) from the polyposal one. The single nasal polyps exhibited glycohistochemical characteristics that differed markedly (p = .0004) from those exhibited by the massive ones. These differences related mainly to the UEA-I, PNA, and the Thomsen-Friedenreich antigen-exposing neoglycoprotein binding characteristics. In conclusion, the present study shows unambiguously that polyposal mucosa, whether of the single or the massive type, exhibits markedly distinct glycohistochemical characteristics when compared to normal nasal mucosa, and that single nasal polyps also differ markedly from massive ones.

Binding Sites↗

Comparison of results of laser and routine surgery therapy in treatment of nasal polyps.

102 patients with nasal polyps receiving ND: YAG laser surgery or routine surgery were followed up for 18-36 months. The postoperative recurrence rates were 40.6% (24/54) and 66.6% (32/48) respectively for the patients of the two groups. Laser surgery is marked by less bleeding, no postoperative packing of the nose and lower postoperative recurrence rate, and it seems to be better than routine removal in the treatment of nasal polyps.

Follow-Up Studies↗

Multifactorial etiology of nasal polyps.

Forty patients with nasal polyps were assessed. Elevated serum total IgE levels in nine patients did not correlate with skin testing. Increased serum immune complexes were detected in 11 patients but did not correlate with depressed complement (five patients). Multiple immunological mechanisms may be involved in nasal polyp formation.

Airway Obstruction↗

The analysis of RCAS1 and DFF-45 expression in nasal polyps with respect to immune cells infiltration.

BACKGROUND: Nasal polyp constitutes a benign growth process in the nasal and sinus mucosa. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a protein expressed mainly by various human cancer cells. It is not only the marker of cancer process and its expression can also be observed in physiological processes. It is responsible for the regulation of immune cells activity. DFF45 (DNA fragmenting factor) has been described as a substrate for caspase-3. DFF45 seems to play an important role in the onset of apoptotic process by acting probably through the regulation of DNA fragmentation. The aim of the study was to evaluate the ability of nasal polyps to regulate the cytotoxic immune response and to determine their resistance to apoptosis. RESULTS: The higher RCAS1 level was identified in lymphocytic nasal polyps, the medium one in eosinophilic while the lowest was identified in neutrophilic. DFF-45 expression was higher in eosinophilic than in neutrophilic and lymphocytic nasal polyps. CONCLUSION: The changes in DFF-45 level in nasal polyps might indicate a different resistance to apoptosis mediated by immune cells. The alterations in RCAS1 expression indicate that nasal polyps have the ability to regulate the cytotoxic immune response. The breaking of resistance to immune mediated apoptosis in nasal polyps might have a new therapeutic impact.

Adult↗

Surgical versus medical treatment of nasal polyps.

Surgical removal of nasal polyps is associated with discomfort and risks for the patient, but is the treatment of choice to most otorhinolaryngologists. Medical treatment alone has been little investigated. In a prospective clinical trial surgical removal followed by continuous topical steroid treatment has been compared with a single dose of steroid deposit followed by continuous topical steroid treatment. During a study period of one year, expiratory nasal peak flow and sense of smell were monitored. In general, the course in the two groups was alike, with a tendency favouring the medically treated group. In another study the clinical efficacy of this medical regimen was further documented experimentally. By acoustic rhinometry the square area of the nasal passages was measured before and a few days after the injection of the steroid deposit. Increased volume was found, corresponding to the instant clinical improvement. It is concluded that primary treatment of nasal polyps should be medical. Surgery is only recommended in cases, resistant to medical therapy.

Administration, Intranasal↗

The ultrastructure of the nasal polyps in patients with and without cystic fibrosis.

Nasal polyps are commonly associated with cystic fibrosis (CF) and also with idiopathic allergies, asthma, and aspirin intolerance. The pathogenesis of nasal polyp formation is controversial. The present study investigates the ultrastructure of thirteen nasal polyps surgically removed from seven CF patients and six non-CF (NCF) patients with allergic diseases, asthma, and aspirin intolerance. All nasal polyps showed focal edema, hyperplasia, atrophy, or squamous metaplasia of the epithelium. The lamina propria was moderately populated with small blood vessels and mucous glands and showed focal accumulation of inflammatory cells. The CF nasal polyps, however, revealed several specific characteristics: 1) minimal damage to the surface epithelium, 2) presence of a mucus blanket lining the apical epithelium, 3) occasional intracytoplasmic lumens, 4) continuous and fenestrated type capillaries, 5) numerous degranulated mast cells, 6) many plasma cells, often with atypical morphology and intracisternal Russell bodies, and 7) a smaller number of eosinophils as compared to the NCF nasal polyps. The results indicate significant differences between CF and NCF nasal polyps and support the multifactorial pathways theory of nasal polyp formation.

Cystic Fibrosis↗